Clonidine and benazoline are two structurally related imidazolines. Whereas clonidine binds both to alpha(2)-adrenoceptors (alpha(2)R) and to I-1 imidazoline receptors (I1R), benazoline showed a high selectivity for imidazoline receptors. Although the alpha(2)R are negatively coupled to adenylate cyclase, no effect on cAMP level by activation of I1R has been reported so far. We therefore aimed to compare the effects of clonidine and benazoline on forskolin-stimulated cAMP levels in cell lines expressing either I1R only (PC12 cells), alpha(2)R only (HT29 cells), or I1R and alpha(2)R together (NG10815 cells). Clonidine proved able to decrease the forskolin-stimulated cAMP level in the cells expressing alpha(2)R and this effect could be blocked by rauwolscine. In contrast, in cells lacking these adrenoceptors, clonidine had no effect. On the other hand, benazoline and other I-1 receptor-selective imidazolines decreased forskolin-stimulated cAMP level in the cells expressing I1R, in a rauwolscine- and pertussis toxin-insensitive manner. These effects were antagonized by clonidine. According to these results, we demonstrated that 1) alpha(2)R and I1R are definitely different entities because they are expressed independently in different cell lines; 2) alpha(2)R and I1R are both implicated in the cAMP pathway in cells (one is sensitive to pertussis toxin and the other is not); and 3) I1R might be coupled to more then one transduction pathway. These new data will be essential to further understand the physiological implications of the I1R and the functional interactions between I-1 receptors and alpha(2)-adrenoceptors.

Coupling of I-1 imidazoline receptors to the cAMP pathway: Studies with a highly selective ligand, benazoline / H., Greney; P., Ronde; C., Magnier; F., Maranca; C., Rascente; W., Quaglia; M., Giannella; M., Pigini; Brasili, Livio; C., Lugnier; P., Bousquet; M., Dontenwill. - In: MOLECULAR PHARMACOLOGY. - ISSN 0026-895X. - STAMPA. - 57:(2000), pp. 1142-1151.

Coupling of I-1 imidazoline receptors to the cAMP pathway: Studies with a highly selective ligand, benazoline

BRASILI, Livio;
2000-01-01

Abstract

Clonidine and benazoline are two structurally related imidazolines. Whereas clonidine binds both to alpha(2)-adrenoceptors (alpha(2)R) and to I-1 imidazoline receptors (I1R), benazoline showed a high selectivity for imidazoline receptors. Although the alpha(2)R are negatively coupled to adenylate cyclase, no effect on cAMP level by activation of I1R has been reported so far. We therefore aimed to compare the effects of clonidine and benazoline on forskolin-stimulated cAMP levels in cell lines expressing either I1R only (PC12 cells), alpha(2)R only (HT29 cells), or I1R and alpha(2)R together (NG10815 cells). Clonidine proved able to decrease the forskolin-stimulated cAMP level in the cells expressing alpha(2)R and this effect could be blocked by rauwolscine. In contrast, in cells lacking these adrenoceptors, clonidine had no effect. On the other hand, benazoline and other I-1 receptor-selective imidazolines decreased forskolin-stimulated cAMP level in the cells expressing I1R, in a rauwolscine- and pertussis toxin-insensitive manner. These effects were antagonized by clonidine. According to these results, we demonstrated that 1) alpha(2)R and I1R are definitely different entities because they are expressed independently in different cell lines; 2) alpha(2)R and I1R are both implicated in the cAMP pathway in cells (one is sensitive to pertussis toxin and the other is not); and 3) I1R might be coupled to more then one transduction pathway. These new data will be essential to further understand the physiological implications of the I1R and the functional interactions between I-1 receptors and alpha(2)-adrenoceptors.
57
1142
1151
Coupling of I-1 imidazoline receptors to the cAMP pathway: Studies with a highly selective ligand, benazoline / H., Greney; P., Ronde; C., Magnier; F., Maranca; C., Rascente; W., Quaglia; M., Giannella; M., Pigini; Brasili, Livio; C., Lugnier; P., Bousquet; M., Dontenwill. - In: MOLECULAR PHARMACOLOGY. - ISSN 0026-895X. - STAMPA. - 57:(2000), pp. 1142-1151.
H., Greney; P., Ronde; C., Magnier; F., Maranca; C., Rascente; W., Quaglia; M., Giannella; M., Pigini; Brasili, Livio; C., Lugnier; P., Bousquet; M., Dontenwill
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/306604
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 58
  • ???jsp.display-item.citation.isi??? 57
social impact